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Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment.
J Pharm Sci. 2019 06; 108(6):2056-2062.JP

Abstract

An amorphous sugar matrix, after drying from an organic solvent, was investigated for use as a method for dispersing hydrophobic drugs (solid dispersion). However, the amorphous sugar, originally contained in the organic solvent, had a significantly low glass transition temperature (Tg), thus rendering it physically unstable. In this study, we examined the physicochemical properties of a sugar in a dried matrix and in an organic solvent, using α-maltose and methanol as a representative sugar and organic solvent. The apparent molar volume of α-maltose was ∼30% smaller in methanol than in water. The methanol-originated amorphous α-maltose exhibited a much greater degree of hydrogen bonding than the water-originated one. Considering these findings, we conclude that the α-maltose maintained its compact conformation in the dried state and consequently caused the markedly low Tg. Second, it was found that heating under appropriate conditions resulted in an increase in the Tg of the methanol-originated amorphous α-maltose as well as a decrease in the level of hydrogen bonding. The aqueous dissolution of 2 model hydrophobic drugs (indomethacin and ibuprofen) from the solid dispersion was also improved as the result of the heat treatment, whereas, to the contrary, the dissolution of another model drug (curcumin) was lowered.

Authors+Show Affiliations

Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: kore@cc.okayama-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30677416

Citation

Takeda, Koji, et al. "Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment." Journal of Pharmaceutical Sciences, vol. 108, no. 6, 2019, pp. 2056-2062.
Takeda K, Sekitoh T, Fujioka A, et al. Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment. J Pharm Sci. 2019;108(6):2056-2062.
Takeda, K., Sekitoh, T., Fujioka, A., Yamamoto, K., Okamoto, T., Matsuura, T., Imanaka, H., Ishida, N., & Imamura, K. (2019). Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment. Journal of Pharmaceutical Sciences, 108(6), 2056-2062. https://doi.org/10.1016/j.xphs.2019.01.008
Takeda K, et al. Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment. J Pharm Sci. 2019;108(6):2056-2062. PubMed PMID: 30677416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment. AU - Takeda,Koji, AU - Sekitoh,Takanari, AU - Fujioka,Akiho, AU - Yamamoto,Kayoko, AU - Okamoto,Takashi, AU - Matsuura,Tsutashi, AU - Imanaka,Hiroyuki, AU - Ishida,Naoyuki, AU - Imamura,Koreyoshi, Y1 - 2019/01/21/ PY - 2018/11/16/received PY - 2019/01/07/revised PY - 2019/01/11/accepted PY - 2019/1/25/pubmed PY - 2020/7/18/medline PY - 2019/1/25/entrez KW - amorphous solid dispersion KW - glass transition temperature KW - heat treatment KW - hydrophobic drug SP - 2056 EP - 2062 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 108 IS - 6 N2 - An amorphous sugar matrix, after drying from an organic solvent, was investigated for use as a method for dispersing hydrophobic drugs (solid dispersion). However, the amorphous sugar, originally contained in the organic solvent, had a significantly low glass transition temperature (Tg), thus rendering it physically unstable. In this study, we examined the physicochemical properties of a sugar in a dried matrix and in an organic solvent, using α-maltose and methanol as a representative sugar and organic solvent. The apparent molar volume of α-maltose was ∼30% smaller in methanol than in water. The methanol-originated amorphous α-maltose exhibited a much greater degree of hydrogen bonding than the water-originated one. Considering these findings, we conclude that the α-maltose maintained its compact conformation in the dried state and consequently caused the markedly low Tg. Second, it was found that heating under appropriate conditions resulted in an increase in the Tg of the methanol-originated amorphous α-maltose as well as a decrease in the level of hydrogen bonding. The aqueous dissolution of 2 model hydrophobic drugs (indomethacin and ibuprofen) from the solid dispersion was also improved as the result of the heat treatment, whereas, to the contrary, the dissolution of another model drug (curcumin) was lowered. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/30677416/Physical_Stability_of_an_Amorphous_Sugar_Matrix_Dried_From_Methanol_as_an_Amorphous_Solid_Dispersion_Carrier_and_the_Influence_of_Heat_Treatment_ DB - PRIME DP - Unbound Medicine ER -